Document Detail


Wild-type offspring of heterozygous prolactin receptor-null female mice have maladaptive β-cell responses during pregnancy.
MedLine Citation:
PMID:  23247113     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Abstract  β-Cell mass increases during pregnancy in adaptation to the insulin resistance of pregnancy. This increase is accompanied by an increase in β-cell proliferation, a process that requires intact prolactin receptor (Prlr) signalling. Previously, it was found that during pregnancy, heterozygous prolactin receptor-null (Prlr(+/-)) mice had lower number of β-cells, lower serum insulin and higher blood glucose levels than wild-type (Prlr(+/+)) mice. An unexpected observation was that the glucose homeostasis of the experimental mouse depends on the genotype of her mother, such that within the Prlr(+/+) group, the Prlr(+/+) offspring derived from Prlr(+/+) mothers (Prlr(+/+(+/+))) had higher β-cell mass and lower blood glucose than those derived from Prlr(+/-) mothers (Prlr(+/+(+/-))). Pathways that are known to regulate β-cell proliferation during pregnancy include insulin receptor substrate-2, Akt, menin, the serotonin synthetic enzyme tryptophan hydroxylase-1, Forkhead box M1 and Forkhead box D3. The aim of the present study was to determine whether dysregulation in these signalling molecules in the islets could explain the maternal effect on the phenotype of the offspring. It was found that the pregnancy-induced increases in insulin receptor substrate-2 and Akt expression in the islets were attenuated in the Prlr(+/+(+/-)) mice in comparison to the Prlr(+/+(+/+)) mice. The expression of Forkhead box D3, which plays a permissive role for β-cell proliferation during pregnancy, was also lower in the Prlr(+/+(+/-)) mice. In contrast, the pregnancy-induced increases in phospho-Jak2, tryptophan hydroxylase-1 and FoxM1, as well as the pregnancy-associated reduction in menin expression, were comparable between the two groups. There was also no difference in expression levels of genes that regulate insulin synthesis and secretion (i.e. glucose transporter 2, glucokinase and pancreatic and duodenal homeobox-1) between these two groups. Taken together, these results suggest that the in utero environment of the Prlr(+/-) mother confers long-term changes in the pancreatic islets of her offspring such that when the offspring themselves became pregnant, they cannot adapt to the increased insulin demands of their own pregnancy.
Authors:
Carol Huang
Related Documents :
6480713 - Transmembrane potential and intracellular potassium ion activity in fetal and maternal ...
22068733 - The pregnant woman with heart disease: management of pregnancy and delivery.
15991013 - Effect of fetal gender on maternal serum human chorionic gonadotropin levels throughout...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-12-17
Journal Detail:
Title:  The Journal of physiology     Volume:  591     ISSN:  1469-7793     ISO Abbreviation:  J. Physiol. (Lond.)     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-03-04     Completed Date:  2013-08-21     Revised Date:  2014-03-07    
Medline Journal Info:
Nlm Unique ID:  0266262     Medline TA:  J Physiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1325-38     Citation Subset:  IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Adaptation, Physiological
Animals
Blood Glucose / metabolism*
Diabetes, Gestational / blood,  genetics,  metabolism*,  pathology
Female
Forkhead Transcription Factors / metabolism
Gene Expression Regulation
Heterozygote*
Insulin / blood*
Insulin Receptor Substrate Proteins / metabolism
Insulin Resistance
Insulin-Secreting Cells / metabolism*,  pathology
Janus Kinase 2 / metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Phosphorylation
Pregnancy
Prenatal Exposure Delayed Effects*
Proto-Oncogene Proteins / metabolism
Proto-Oncogene Proteins c-akt / metabolism
Receptors, Prolactin / deficiency*,  genetics
Repressor Proteins / metabolism
Signal Transduction
Tryptophan Hydroxylase / metabolism
Chemical
Reg. No./Substance:
0/Blood Glucose; 0/Forkhead Transcription Factors; 0/Foxd3 protein, mouse; 0/Foxm1 protein, mouse; 0/Insulin; 0/Insulin Receptor Substrate Proteins; 0/Irs2 protein, mouse; 0/Men1 protein, mouse; 0/Proto-Oncogene Proteins; 0/Receptors, Prolactin; 0/Repressor Proteins; EC 1.14.16.4/Tph1 protein, mouse; EC 1.14.16.4/Tryptophan Hydroxylase; EC 2.7.10.2/Jak2 protein, mouse; EC 2.7.10.2/Janus Kinase 2; EC 2.7.11.1/Proto-Oncogene Proteins c-akt
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Age-dependent chloride channel expression in skeletal muscle fibres of normal and HSA(LR) myotonic m...
Next Document:  A prospective randomized longitudinal study involving 6 months of endurance or resistance exercise. ...